The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens

被引:77
作者
Fritz, JH
Brunner, S
Birnstiel, ML
Buschle, M
Gabain, AV
Mattner, F
Zauner, W
机构
[1] Intercell AG, A-1030 Vienna, Austria
[2] Univ Vienna, Inst Microbiol & Genet, A-1030 Vienna, Austria
关键词
innate immunity; vaccination; depot of antigen;
D O I
10.1016/j.vaccine.2004.03.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cationic antimicrobial peptides (CAMPs) are active defence components of the innate immune system. Several artificial CAMPs have been designed as antibiotic peptide therapeutics, but none have been reported to exert adjuvant activity in animal models. Here we show for the first time that an artificial CAMP, KLKLLLLLKLK (KLKL5KLK), is a potent inducer of adaptive immunity to co-injected antigens in vivo. High levels of antigen-specific antibodies were obtained after co-injection of KLKL5KLK with the model antigen ovalbumin (OVA) or a commercially available influenza vaccine. We show that KLKL5KLK induces a sustained immune response with a prevalent T(H)2 profile when co-injected with proteinaceous and peptide-based antigens. Furthermore, the immuno-enhancing activity of peptide KLKL5KLK was retained when C-terminally amidated or synthesised as retro-all-D-peptide. We provide evidence that KLKL5KLK enhances the association of antigen to antigen-presenting cells and forms a depot of antigen at the site of injection, making it an interesting adjuvant for novel vaccine design. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3274 / 3284
页数:11
相关论文
共 41 条
  • [1] NOVEL SYNTHETIC ANTIMICROBIAL PEPTIDES EFFECTIVE AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS
    ALVAREZBRAVO, J
    KURATA, S
    NATORI, S
    [J]. BIOCHEMICAL JOURNAL, 1994, 302 : 535 - 538
  • [2] Immunobiology of dendritic cells
    Banchereau, J
    Briere, F
    Caux, C
    Davoust, J
    Lebecque, S
    Liu, YT
    Pulendran, B
    Palucka, K
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 : 767 - +
  • [3] Innate immunity and the normal microflora
    Boman, HG
    [J]. IMMUNOLOGICAL REVIEWS, 2000, 173 : 5 - 16
  • [4] INDUCTION OF OVALBUMIN-SPECIFIC CYTO-TOXIC T-CELLS BY INVIVO PEPTIDE IMMUNIZATION
    CARBONE, FR
    BEVAN, MJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (03) : 603 - 612
  • [5] Activation of human neutrophils by a synthetic anti-microbial peptide, KLKLLLLLKLK-NH2, via cell surface calreticulin
    Cho, JH
    Homma, K
    Kanegasaki, S
    Natori, S
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 266 (03): : 878 - 885
  • [6] Cho JH, 2001, CELL STRESS CHAPERON, V6, P148, DOI 10.1379/1466-1268(2001)006<0148:AOHMCL>2.0.CO
  • [7] 2
  • [8] Cutting edge:: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity
    Cole, AM
    Ganz, T
    Liese, AM
    Burdick, MD
    Liu, L
    Strieter, RM
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 167 (02) : 623 - 627
  • [9] Crustacean immunity -: Antifungal peptides are generated from the C terminus of shrimp hemocyanin in response to microbial challenge
    Destoumieux-Garzón, D
    Saulnier, D
    Garnier, J
    Jouffrey, C
    Bulet, P
    Bachère, E
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) : 47070 - 47077
  • [10] Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system
    Gudmundsson, GH
    Agerberth, B
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1999, 232 (1-2) : 45 - 54